Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases
Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases
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DOI：
10.1016/j.cell.2021.03.056
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发表时间：
2021-05-27
期刊：
影响因子：
64.5
通讯作者：
Fujio, Keishi
中科院分区：
文献类型：
--
作者：
Ota, Mineto;Nagafuchi, Yasuo;Fujio, Keishi
遗传学研究揭示了许多与免疫介导性疾病相关的变异基因。为了阐明疾病的发病机制，有必要了解这些变异的功能，特别是在疾病相关的条件下。在这里，我们进行了大规模的免疫细胞基因表达分析，同时进行了全基因组序列分析。我们的数据集包括来自337名被诊断为10类免疫介导性疾病的患者和79名健康志愿者的28个不同的免疫细胞亚群。我们的数据集捕获了不同免疫细胞类型和疾病的独特基因表达谱。表达数量性状基因座(EQTL)分析揭示了eQTL效应在免疫条件和细胞类型方面的动态变化。这些特定于细胞类型和上下文相关的eQTL在免疫疾病相关的遗传变异中表现出显著的丰富，它们与疾病相关的细胞类型、基因和环境有关。这份图谱加深了我们对体内疾病条件下疾病相关变体的免疫遗传功能的理解。
Genetic studies have revealed many variant loci that are associated with immune-mediated diseases. To elucidate the disease pathogenesis, it is essential to understand the function of these variants, especially under disease-associated conditions. Here, we performed a large-scale immune cell gene-expression analysis, together with whole-genome sequence analysis. Our dataset consists of 28 distinct immune cell subsets from 337 patients diagnosed with 10 categories of immune-mediated diseases and 79 healthy volunteers. Our dataset captured distinctive gene-expression profiles across immune cell types and diseases. Expression quantitative trait loci (eQTL) analysis revealed dynamic variations of eQTL effects in the context of immunological conditions, as well as cell types. These cell-type-specific and context-dependent eQTLs showed significant enrichment in immune disease-associated genetic variants, and they implicated the diseaserelevant cell types, genes, and environment. This atlas deepens our understanding of the immunogenetic functions of disease-associated variants under in vivo disease conditions.